TABLE 3

Intrinsic clearance ranges for 72 reference compounds metabolized by cytochrome P450 enzymes

CYP3A4 substrates: alprazolam, amitriptyline, bepridil, bupivacaine, buprenorphine, buspirone, chlorpheniramine, chlorpromazine, clomipramine, clozapine, diazepam, diclofenac, diltiazem, domperidone, fentanyl, fluphenazine, glimepiride, glyburide, haloperidol, imipramine, ketamine, lidocaine, lormetazepam, mepivacaine, mianserin, midazolam, nalbuphine, naloxone, ondansetron, perphenazine, prazosin, prochlorperazine, promazine, promethazine, propafenone, quinidine, quinine, risperidone, sildenafil, trazodone, triazolam, trimipramine, verapamil, zaleplon, zolpidem.

CYP2D6 substrates: alprenolol, amitriptyline, bepridil, betaxolol, buspirone, chloroquine, chlorpheniramine, chlorpromazine, clomipramine, clonidine, clozapine, desipramine, diphenhydramine, fluoxetine, fluphenazine, fluvoxamine, imipramine, labetalol, levoprotiline, maprotiline, meptazinol, metoclopramide, metoprolol, mexiletine, mianserin, nortriptyline, ondansetron, oxprenolol, perphenazine, pindolol, prochlorperazine, promazine, promethazine, propafenone, propranolol, (–)-propranolol, (+)-propranolol, risperidone, timolol, trazodone, trimipramine.

CYP2C9 substrates: Diclofenac, flurbiprofen, gemfibrozil.

CYP1A2 substrates: amitriptyline, chlorpromazine, clomipramine, clozapine, mexiletine, phenacetin, promazine, promethazine, propranolol, tacrine.

CYP2C19 substrates: alprenolol, amitriptyline, bepridil, bupivacaine, chlorpromazine, clomipramine, clozapine, desipramine, fluvoxamine, imipramine, labetalol, mexiletine, mianserin, nalbuphine, perphenazine, prochlorperazine, promazine, propafenone, (–)-propranolol, (+)-propranolol, scopolamine, tocainide, trimipramine.

Not metabolized: acebutolol, acetaminophen, amiodarone, amrinone, antipyrine, atenolol, bumetanide, carbamazepine, chlorpropamide, clofibric acid, cocaine, fenoprofen, flecainide, flumazenil, furosemide, gliclazide, glipizide, ibuprofen, isoxicam, ketoprofen, ketorolac, lorazepam, montelukast, morphine, nadolol, nitrazepam, oxazepam, practolol, procainamide, sulfinpyrazone, sulpiride, temazepam, tenoxicam, tolbutamide, trimethoprim, warfarin.


Enzyme

%Drugs Metabolized

CLint
Mean ± S.D.
Range (-Fold Difference)
μl/min/pmol P450
CYP3A4 41 4.5 ± 5.6 0.3-21 (70)
CYP2D6 37 5.7 ± 9.9 0.6-60 (100)
CYP2C19 21 1.6 ± 1.7 0.4-8.1 (21)
CYP1A2 9 1.1 ± 0.8 0.4-2.5 (6)
CYP2C9
3
2.8 ± 3.1
0.9-6.4 (7)